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PDGFRPlatelet Derived Growth Factor Receptor
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Imatinib may cause vasodilatation and fluid retention due to inhibition of the PDGFR kinase that regulates interstitial fluid pressure.
The problem with targeting normal receptors such as EGFR and PDGFR, is that even though they are expressed at high levels in cancer cells, they are also expressed in some normal tissues.
PDGFR expression in differential diagnosis between KIT-negative gastrointestinal stromal tumours and other primary soft-tissue tumours of the gastrointestinal tract.
The presence of the rearrangements in the PDGFR gene suggest that these specific tumors have evolved to be dependent on signaling through this receptor, a target for several drugs under development.
Several chemotherapy agents, including Sutent(r) (sunitinib), Nexavar(r) (sorafenib) and Gleevec(r) (imatinib), work by targeting and inhibiting PDGFR.
Aarif Khakoo and colleagues have now identified a role for PDGFR-beta in mouse heart muscle cells that might help explain why inhibitors of PDGFR signaling can cause heart failure.
Our findings also suggest that sunitinib or imatinib, but not sorafenib, may be preferable to tyrosine kinase inhibitors in this patient population, as we detected expression of cKIT but not of PDGFR.
The first study, "Ponatinib, a potent pan-BCR-ABL inhibitor, retains activity against gatekeeper mutants of FLT3, RET, KIT, PDGFR and FGFR1," was presented yesterday and shows that ponatinib overcomes resistant gatekeeper mutations well beyond BCR-ABL -- the drug's target in chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) -- in other clinically relevant tyrosine kinase targets.
Aberrant Regulation of PDGFs & PDGFR in Solid Tumors II-36
The substance simultaneously inhibits three growth factors and receptors that play an important role in angiogenesis: VEGFR, PDGFR and FGFR.
In addition, Array continues to work on advancing two preclinical collaboration targets: TYK2 inhibitors for the treatment of inflammatory disease and PDGFR inhibitors for the treatment of fibrosis.
Telatinib is a potent oral kinase inhibitor that selectively targets VEGFR, PDGFR and KIT receptor tyrosine kinases.